Disease: Multiple Sclerosis
Type of study: Interventional trial
Coordinating investigator: Øivind Torkildsen
Study director: Kjell-Morten Myhr
Background: B-cell depletion therapy is highly effective in relapsing-remitting MS. Rituximab seems to have comparable efficacy and safety profile to ocrelizumab, but data on optimal dosing is limited and largely based on various off-label regimes. The most frequent used dosing regimen in Norway (until recently) has been a single starting dose of 1000 mg infusion, followed by 500 mg infusions every six months for an undefined time. The therapy seems safe, and limited side effects are reported, where neutropenia, lymphopenia, hypogammaglobulinemia and infections are the most frequent adverse events. Real world experience indicates that B-cells may be depleted for a longer period, even for at least 12 months, and longer dosing intervals than six months (e.g., due to intercurrent illness or pregnancy planning) seems safe. Based on these observations, clinical practice in Norway is changing to extended dosing intervals after at least two years of therapy. In this study, we aim to investigate the efficacy and safety of extending the dosing interval from 6 to 12 months in RRMS.
All patients finishing the OVERLORD-MS study that have been stable without new MRI or clinical disease activity for at least two years will be offered an extension of further rituximab (500 mg) dosing interval from 6 to 12 months interval.
The objectives of the study are to evaluate whether the efficacy and safety of 12-months dosing of rituximab is equal to the standard six months interval.
Design: This is a prospective observational open label trial comparing the efficacy and safety of standard interval dosing (SID – of six months) to extended interval dosing (EID – of twelve months) of rituximab in relapsing-remitting MS patients. The patients will be their own controls by comparing previous SID period to later EID period in each patient.
The primary endpoint of the study is the proportion of patients with no evidence of disease activity (NEDA) after 2 years.
Status: The study will prospectively recruit patients that have finished the OVERLORD-MS study period, including the following switch period of 6 months.
Participating centres
Norway
- Haukeland University Hospital, Bergen
- Oslo University Hospital, Oslo
- Akershus University Hospital, Lørenskog
- Stavanger University Hospital, Stavanger
- University Hospital of North Norway, Tromsø
- Nordland Hospital Trust, Bodø
- Namsos Hospital Trust, Namsos
- Molde Hospital Trust, Molde
- Sørlandet Hospital Trust, Kristiansand
- Telemark Hospital Trust, Skien
- Vestre Viken Hospital Trust, Drammen
Sweden
- Karolinska Institute, Stockholm
Funding
- The Research Council of Norway, Neuro-SysMed
- The Regional Health Authority of Western Norway
- Haukeland University Hospital
- The University of Bergen
- The DAM foundation
- Participating hospitals